1. Bennett R. Curr Pain Headache Rep 8(5):379-384, 2004.
Aalborg University, Denmark
Award Amount (September 2008): $30,000
Hong-You Ge, M.D., Ph.D., and his colleagues at Aalborg University in Denmark, plan to evaluate 30 FMS patients and 30 healthy age-matched control subjects for the presence of active and latent MTPs. Initially the MTPs and their referred pain patterns will be identified by careful palpation of the muscles in the neck, shoulders, low back, and extremities. The pressure pain thresholds at all MTPs will also be measured. An anatomical map of the latent and active MTPs, as well as the areas of referred pain will be generated for each subject. Ge’s team also will confirm the presence of each MTP by measuring its electrical activity with electromyography (EMG).
In a second session one week later, subjects will be evaluated at the 18 diagnostic tender areas for FMS. Ge will look for the presence of latent or active MTPs at or near the 18 tender points. He will also determine if any of the tender points are located in an area of referred pain generated by an MTP. In addition, the MTPs will be confirmed by EMG. Since a tender point exam is done to identify areas of lowered pain threshold and MTPs have been documented to cause a lowering of pressure pain thresholds, it’s plausible that the 18 tender points might possibly be MTPs, but this has never been explored.
To fully assess the extent to which MTPs contribute to the generalized pain of FMS, Ge proposes to look at the impact of treating the MTPs in “Part 2” of his study. Upon successful completion of the evaluation phase, AFSA has already pre-approved the funding of Ge’s treatment phase. Obviously, if effective treatment of the MTPs does lead to significant pain and symptom relief, this would provide important evidence of the role of MTPs in FMS and will prompt increased education on the treatment of MTPs.
Principal Investigator: César Fernández de las Peñas, P.T., Ph.D.
César Fernández de las Peñas, P.T., Ph.D., and his colleagues in Spain, propose to evaluate the role of MTPs in generating FMS symptoms using a different approach from that of Ge’s team. Fifty FMS patients and 50 healthy age-matched controls will be carefully examined for the presence of active and latent MTPs. The referred pain patterns of each active MTP will also be charted. Muscles in the head, neck, shoulders, back, buttocks, legs, and forearms will be physically assessed for the presence of firm nodules and pain tenderness to identify the MTPs and their associated referral pain patterns. This will provide insight about each person’s peripheral pain generators in their muscles.
All subjects will undergo sensory pain testing to determine thresholds to pressure, cold, and heat pain. Muscles throughout the body will be used in these tests, which are designed to reflect impairments in the central nervous system’s ability to process pain. In addition, participants will fill out validated questionnaires to assess quality of life, physical functioning, and pain severity.
Statistical analyses will be performed to determine how the number of active and latent MTPs influence the sensory processing system, quality of life, functional ability, and overall pain severity.
The 18 diagnostic tender points will also be assessed to determine if any of the tender points are nearby active or latent MTPs, or in an area of referred pain that is produced by an active MTP. The goal of this part of the study is the same as that of Ge’s, because it will take more than one research team or medical journal report to draw attention to the possible overlap between the diagnostic tender points of FMS and the presence of MTPs.
Several memory and mental processing tests show that fibromyalgia syndrome (FMS) patients have good reason to be complaining about their cognitive function, or what is called “fibro fog.” Putting your thought processes into perspective, one study showed that you are functioning at a level that is 20 years older than your actual age.1 Not surprisingly, last year M. Catherine Bushnell, Ph.D., of McGill University in Montreal, Canada, reported a premature loss of gray matter in several areas of the brain involved in pain and memory processing.2 The study was small and compared ten FMS patients to ten healthy pain-free control subjects (all women and age-matched to reduce variability).
As a person with FMS, you most likely want to know what the loss in gray matter means. Is it linked to your symptoms of pain? Does it correspond to your cognitive dysfunction? Or, perhaps loss of gray matter is tied to many symptoms. The initial study showed that gray matter loss increased with duration of symptoms, so a study involving a larger number of subjects is certainly warranted.
“It is well documented that cognitive functions, such as speed of information processing, working memory, and long-term memory, decline continuously across the adult life span beginning in the second decade of life,” says Bushnell. “So an obvious question arising from our preliminary findings is: ‘What is the relationship between accelerated brain aging in FMS patients and cognitive function?’ To answer this question, our study will examine the relationship between brain anatomy and different measures of cognitive functioning in 30 non-depressed, medication-free FMS patients. We will test the hypothesis that FMS patients have an increased age-related decline in cognitive functioning. We will determine the degree of dysfunction and the amount of gray matter loss relative to 30 age-matched control subjects.”
Other important goals of the study will be to determine if loss of gray matter correlates with:
It’s essential that fatigue or alertness be excluded as the cause of the cognitive difficulties in FMS patients. Given that widespread pain is present in all patients, how is this symptom related to the loss of gray matter and cognitive dysfunction? Could pain be distracting or interfering with a person’s ability to process information? Also, how does the gray matter loss relate to a patient’s functional ability (or disease severity) and duration of symptoms?
Answers to these questions are needed to better characterize the significance of the gray matter loss, as well as the interrelationships between pain, fatigue, physical function, and cognitive abilities. If accelerated gray matter loss is found to correlate with diminished cognitive function, then efforts must be placed on early identification of FMS as well as testing therapies that can reduce or reverse the structural changes in the brain.
1. Park DC, et al. Arthritis Rheum 44(9):2125-33, 2001.
What could be the possible genetic underpinnings of fibromyalgia syndrome (FMS)? Manuel Martinez-Lavin, M.D., of the National Institute of Cardiology in Mexico City, believes that the sympathetic nervous system (the body’s “fight-or-flight” stress response) is the source of your many symptoms. In addition, he has found that FMS is related to genetic factors that alter the function of the sympathetic branch of the autonomic nervous system, which consists of the sympathetic and parasympathetic systems.
Martinez-Lavin’s published, AFSA-funded study evaluates variations in the genes that regulate the speed of the catechol-O-methyltransferase (COMT) enzyme.1 Dopamine, norepinephrine, and epinephrine are all broken down by the COMT enzyme so they can be eliminated by the body. Genetic abnormalities that lead to an excessively slow or “sluggish” COMT enzyme will cause accumulation of norepinephrine and epinephrine, the two transmitting substances used by the sympathetic nervous system. As a result, FMS could be due to sympathetic hyperactivity with a genetic component.
Referring to a study of 202 healthy women, Martinez-Lavin comments, “Women who slowly degraded the catecholamines are more sensitive to pain.” He adds that there are six known variations in the COMT gene that can lead to a slow-working enzyme and make a person more susceptible to developing a facial-jaw pain condition called temporomandibular dysfunction or TMD.2
Different ethnic factors may also influence the variations in the COMT gene, so Martinez-Lavin looked at two populations: women from Mexico and women from Spain. He found a higher incidence of three alterations in the COMT gene in the Spanish FMS patients that distinguished them from healthy controls (80 FMS patients versus 80 control subjects).
“In the Spanish people, there was a clear relationship between the number of defects in the COMT gene and FMS severity, according to the Fibromyalgia Impact Questionnaire (FIQ),” says Martinez-Lavin. Whereas, in the Mexican population, there was only a slight correlation with two sub-scales of the FIQ.” In other words, the Spanish patients with FMS had a sluggish COMT enzyme related to genetic glitches, while the Mexican FMS patients were not that different from the control subjects.
Both the Spanish and Mexican patients had very similar FIQ scores, meaning that they were equally impacted by their FMS. This leads Martinez-Lavin to go one step further to look at the adrenergic receptors that are activated by norepinephrine and epinephrine (the two chemical transmitters that build up when the COMT is slow). He hypothesizes that genetic alterations may cause the adrenergic receptors to become highly sensitized in the Spanish and Mexican FMS patients—similar to findings in women with TMD.3 He is currently testing this possibility.
As a patient, what does this mean for you? Regardless of whether you have genetic defects in your COMT enzyme or adrenergic receptors, the end result is a malfunctioning sympathetic nervous system that causes pain and many other symptoms. However, “Genetic make-up, partially influenced by ethnicity will play a role in therapy,” says Martinez-Lavin. “This is what pharmacogenetics is all about. As an example, a person with a COMT enzyme that slowly degrades norepinephrine may have important side effects from antidepressant medications that increase norepinephrine levels.” Overall, therapies that calm down the sympathetic system should lead to symptom improvements, such as adrenergic receptor blockers, many anti-epileptic medications, benzodiazepines, biofeedback/relaxation, yoga, tai chi, etc.
1. Vargas-Alarcon C, et al. Arthritis Res Therapy 9:R110, 2007.
The criteria for fibromyalgia syndrome (FMS) does not convey how severely impacted a person is with this condition. In fact, the diagnostic criteria are not completely objective and two patients with all 18 tender points may be differently affected by their FMS. Having a marker that reflects illness severity would be beneficial.
A chemical referred to as NAA appears to correlate with disease severity and can be detected by magnetic resonance spectroscopy (MRS) in the hippocampus region of the brain, according to Patrick Wood, M.D.1 “I suspect that eventually NAA may become a biomarker that allows us to track and demonstrate changes in the clinical profile” of a person with fibromyalgia, says Wood.
As another part of his AFSA-funded study, Wood also demonstrated significant gray matter loss in several brain regions.2 Given the somewhat scary nature of these findings, it is important to have a disease marker that shows objective changes in brain function. With more research, low NAA levels or some other substance is bound to show up as a marker.
1. Wood PB, et al. J Pain [Epub ahead of print] Sept. 2, 2008.
The American Fibromyalgia Syndrome Association, Inc. (AFSA)
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